Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0043167 (pertussis)
 19,595 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Multiple sclerosis (MS) and its animal model experimental autoimmune encephalomyelitis (EAE) are marked by inflammatory demyelinating lesions throughout the central nervous system, including optic nerve. Neuronal loss also occurs in EAE, including retinal ganglion cell (RGC) loss in eyes with optic neuritis, but the finding of RGC loss in relation to optic nerve inflammation differs in different EAE settings. Recently, Myelin oligodendrocyte glycoprotein (MOG)-specific TCR transgenic mice were found to develop spontaneous isolated optic neuritis in the absence of EAE. In the current study, the relationship of inflammation to retinal ganglion cell (RGC) loss during isolated optic neuritis is examined. RGCs of MOG-specific TCR transgenic mice were labeled with Flourogold and then treated with pertussis toxin (PT) or observed untreated. At various time points, RGCs were counted, retinas were TUNEL labeled, and optic nerves were examined for inflammatory cell infiltrates. 29% of untreated MOG-specific TCR transgenic mice developed periocular inflammation by 4 months of age, and 32% of optic nerves of TCR transgenic mice had histological lesions in the optic nerve. Incidence of histological optic neuritis was 20% at day 8 following injection of PT and increased to 48% by day 12, and 68% by day 16. In contrast, no RGC loss or TUNEL staining was detected in eyes with optic neuritis until day 12 in the mice injected with PT. A 28% reduction in RGC numbers at day 12 increased to 39% by day 16, and RGC loss of eyes with severe or massive inflammation was significantly higher than that of eyes with mild or moderate inflammation. No RGC loss occurred in TCR transgenic mouse eyes without optic neuritis. The fact that inflammation precedes RGC loss suggests that neuronal loss during optic neuritis occurs secondary to the inflammatory process in isolated optic neuritis.
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PMID:Retinal ganglion cell damage induced by spontaneous autoimmune optic neuritis in MOG-specific TCR transgenic mice. 1682 69

Myelin oligodendrocyte glycoprotein peptide fragment 35-55 (MOG35-55) is a major autoantigen inducing experimental autoimmune encephalomyelitis, an animal model of multiple sclerosis that is characterized by blood-brain barrier (BBB) disruption. Various experimental approaches have employed MOG35-55 in vivo; however, in vitro BBB models using MOG35-55 are rarely reported. We investigated MOG35-55 exposure effects with complete Freund's adjuvant (CFA) and pertussis toxin (PTX) on brain endothelial cells and elucidated the relationships among NADPH oxidase, MMP-9, ICAM-1, and VCAM-1. These 4 factors significantly increased in MOG35-55+CFA+PTX-exposed endothelial cells compared with the control cells. NADPH oxidase inhibition using apocynin reduced MMP-9 activity, ICAM-1, and VCAM-1. MMP-9 inhibitor I decreased expression of ICAM-1 and VCAM-1, and both anti-ICAM-1 and anti-VCAM-1 inhibited MMP-9 activity. Inhibitions of MMP-9, ICAM-1, and VCAM-1 did not change NADPH oxidase activity. Although inhibition of these 4 factors decreased BBB permeability in cells, inhibition of NADPH oxidase exhibited the highest decrease among these. NADPH oxidase directly influenced MMP-9, ICAM-1, and VCAM-1, but not vice versa. MMP-9 and the cell adhesion molecules reversibly affected each other. In conclusion, NADPH oxidase-derived superoxide elevated expression of MMP-9, ICAM-1, and VCAM-1, and these interactions can finally result in increases of BBB permeability in MOG35-55+CFA+PTX-exposed endothelial cells.
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PMID:A leading role for NADPH oxidase in an in-vitro study of experimental autoimmune encephalomyelitis. 2692 15